SUMMARY: Charcot-Marie-Tooth disease (CMT) is a family of inherited peripheral neuropathies. CMT is characterized by progressive weakness, imbalance, sensory loss, and gait abnormalities. Multiple promising candidate therapies will be ready for human clinical trials within 5 years. We in the Inherited Neuropathies Consortium Rare Disease Clinical Research Network (INC RDCRN) have defined the natural history of CMT1A and this research continues in other CMT subtypes. The INC RDCRN has also led development of multiple, clinical outcome assessments and patient-reported outcome measures for children and adults with CMT. Individuals with CMT identify impairments in gait and balance as highly impacting their quality of life and therefore therapeutic interventions that positively impact these functions are likely to be meaningful. In preparation for clinical trials in CMT, some critical gaps in trial readiness must be urgently filled including precise knowledge of real world physical activity in individuals with different types of CMT and the effect of disease progression on physical activity. Sensitive biomarkers of gait and balance dysfunction are also needed for early phase trials to detect signals of therapeutic effect. Research at INC sites using 3D motion analysis laboratories suggests that gait parameters, including gait speed and stride length, are highly responsive to change in individuals with CMT. 3D motion analysis laboratories are however not viable for multicenter trials. Wearable technology including activity monitors and inertial sensors is easily applied and suitable to measure physical activity, gait and balance in multicenter studies involving children and adults. Clinical Research Project 3, ?Wearable Sensor Measures for Physical Activity, Gait and Balance in CMT?, addresses these gaps of clinical trial readiness. The aims of this project include: (1) Characterization of real world function in CMT by measuring habitual physical activity of children and adults with the most common genetic subtypes. (2) Validation of ?digital biomarkers? of gait and balance deficits in CMT by assessment of the reliability and responsiveness to change of wearable sensors. Dr. J. Burns (U. Sydney) and Dr. K. Eichinger (U. Rochester) will co-lead this study. Drs. Burns, Pareyson, and V. Ounpuu have extensive experience in quantitative gait analysis in CMT. Dr. Eichinger, T. Estilow and Dr. Ramdharry have expertise in assessing physical activity, mobility and balance in CMT. Drs. Shy (INC RDCRN PI, U. Iowa), Reilly (site PI, U. College of London), Scherer (site PI, U. Pennsylvania), Yum (Children?s Hospital of Philadelphia), Ascadi (Connecticut Children?s Hospital) and Herrmann (Clinical Team Liason, site PI, U. Rochester) have vast experience in clinical aspects and outcome measure development in CMT. This study brings together a leading group of CMT investigators who have a long history of collaboration, and should yield outcome measures that will have a high impact on conducting early and late phase clinical trials in CMT for which no disease-modifying therapy is yet available.